With advancing age, the bone mass decreases. In the younger generation, calcium in bones may also be congenitally or idiopathically abnormally absorbed in blood, so that calcium in bones is reduced and the bone mass is hence lowered, resulting in imperfect bone metabolism and osteogenesis.
Disordered bone metabolism and osteogenesis will bring about fracture, osteomalacia, osteoporosis and/or low back pain. In recent years, the aged people are rapidly increasing in the world and osteogenesis imperfecta increases correspondingly. Also, similar diseases are increasing in the younger generation due to calcium deficiency caused by the disproportionately eating habit.
Experimental markers for osteogenesis and calcification include measurements or determinations of calcium content, alkaline phosphatase activity and DNA content in bones. It is said that the formation and metabolism of bones are more active as these contents or levels in the bone increase.
Calcitonin and active vitamin D.sub.3 drugs have heretofore been used generally in medicinal therapy of diseases caused by imperfect osteogenesis. Besides, hormone drugs and calcium preparations are also used.
Although the calcitonin shows an excellent effect on pains in osteoporosis, it does not exhibit any effects when orally administrated because it is a peptide. Its only use as an injection is however accompanied by problems of inconvenient administration and pain upon its administration. On the other hand, the active vitamin D.sub.3 drugs are insufficient in effects such as bone-forming action and pain-alleviating action and involve such problems as bring about hypercalcemia.
Further, it has been shown in vivo [Metabolism, 35, 1044-1047 (1986); and Biochem. Pharmacol., 35, 773-777 (1986)] and in vitro [Biochem. Pharmacol., 36, 4007-4012 (1987); and ibid., 37, 4075-4080 (1988)] that zinc plays an important role as an activator for stimulation and calcification in osteogenesis. Furthermore, it has been shown that zinc stimulates bone protein synthesis [Biochem. Parmacol., 37, 4075-4080 (1988)].
However, pharmaceutical use of zinc has not been attained though it has been suggested that it has osteogenesis-accelerating action. Zinc itself involves a problem in points of absorption, metabolism and toxicity. There has thus been a demand for the development of a substance excellent in bone-forming property.
On the other hand, an L-carnosine zinc salt is a zinc salt of L-carnosine derived from beta-alanine and L-histidine. The salt has been known to have peptic ulcer-healing action (Japanese Patent Application Laid-Open No. 33270/1984) and preventing and healing action of hepatopathy (Japanese Patent Application Laid-Open No. 14728/1988). It has been suggested that inhibition of free-radical reaction (anti-active-oxygen action) participates in mechanism of anti-ulcer action [Journal of Japanese Digestive Disease Society, 85. Extra edition, 644 (1987)]. It has however been not known that the zinc salt or complex of L-carnosine has osteogenesis-accelerating action.
With the foregoing circumstances in view, the present inventors have carried out an extensive investigation. As a result, it has been found that the zinc salt or complex of L-carnosine has excellent osteogenesis-accelerating action, and an osteogenesis-accelerating agent comprising, as an active ingredient, this compound is extremely low in toxicity and side effects and useful in treating fracture, osteomalacia and the like, which are caused by a disorder of bone metabolism or osteogenesis, leading to completion of the present invention.